P-187 Epidermal growth factor receptor inhibitors (EGFRi) in patients with left-side, RAS wildtype metastatic colorectal cancer: Clinician use and outcomes for patients
Authors: J. McKenzie, S. Kosmider, R. Wong, Y. To, J. Shapiro, C. Dunn, M. Burge, W. Hong, S. Caird, S. Lim, H. Wong, B. Lee, P. Gibbs, V. Wong
Journal: Annals of Oncology (2022)

Current treatment for metastatic colorectal cancer (mCRC), includes anti-epidermal growth factor receptor inhibitors (EGFRi) for RAS wildtype cancers. With improved outcomes has come added complexity for clinician treatment selection and sequencing. Head-to-head studies support first-line EGFRi use over bevacizumab in combination with chemotherapy for patients with a left-side primary. In January 2015, the EGFRi cetuximab gained government approval for first-line use in Australia, with routine RAS testing increasing in turn. In clinical practice, around 50% of patients do not receive second-line treatment, suggesting many patients miss out on this treatment option if reserved for second-line and later treatment. Clinical data from July 2009 to July 2021 was reviewed from TRACC (Treatment of Recurrent and Advanced Colorectal Cancer), a prospective, comprehensive, multi-site Australasian registry, to identify patients with RAS wildtype, left-side primary mCRC who received first-line treatment. Intent (curative vs palliative), biologic use and chemotherapy backbone were described over time. Patients who received first-line palliative intent doublet chemotherapy who were ECOG 0 or 1 at diagnosis were further characterised. Second-line treatment groups were analysed according to biologic and sequence used. Fisher's exact test was used for significance tests and Kaplan Meier curves for survival analyses. 800 patients had left-side primary RAS wildtype mCRC and received first-line chemotherapy. 166 (20%) received first-line EGFRi plus chemotherapy, 352 (43%) received bevacizumab plus chemotherapy, and 282 (35%) received chemotherapy alone. Patients diagnosed after government EGFRi approval in January 2015 were more likely to be treated with first-line EGFRi plus chemotherapy than first-line bevacizumab plus chemotherapy (36% vs 30%, p < 0.001). While patients receiving first-line EGFRi were younger (60 vs 62 years, p=0.006) with fewer comorbidities (Charlson Comorbidity Index ≥ 3 in 13% vs 20%, p=0.048), ECOG status, de novo metastatic disease, deficient mismatch repair status or site of metastases were not different between the two groups. Overall, 148 (19%) left-side primary RAS wildtype patients never received any biologic agent. Of the palliative intent cohort (n = 490), median progression-free survival (PFS) was 11.6, 10.5 and 9.2 months for EGFRi plus doublet chemotherapy, bevacizumab plus doublet chemotherapy, and doublet chemotherapy alone respectively. EGFRi plus doublet chemotherapy had significantly longer PFS than doublet chemotherapy alone (HR 0.70 [0.52 - 0.95], p=0.022), but did not reach statistical significance compared to the bevacizumab group. However, median overall survival for the palliative intent cohort was significantly improved in the EGFRi group compared to bevacizumab group (53.2 vs 30.0 months; HR 0.70 [0.52 – 0.95]). When sequencing agents at progression, second-line PFS trended longer for those receiving EGFRi then bevacizumab, as compared to those receiving bevacizumab then EGFRi (7.9 vs 6.0 months; p=0.25). In this community series, first-line EGFRi plus doublet chemotherapy significantly improved OS when compared with bevacizumab plus doublet chemotherapy for left-side RAS wildtype mCRC patients. This was despite not demonstrating a PFS benefit in first-line, suggesting treatment sequencing may impact biologic efficacy. Despite EGFRi use increasing over time, 1 in 5 patients with left-side RAS wildtype mCRC never received any biologic agent.